{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T19:55:36Z","timestamp":1762113336897},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,7,19]],"date-time":"2012-07-19T00:00:00Z","timestamp":1342656000000},"content-version":"vor","delay-in-days":7627,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1991,9]]},"abstract":"<jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Whole\u2010cell, patch\u2010clamp recordings from cultured hippocampal neurones have been used to characterize the action of the GABA<jats:sub>A<\/jats:sub> ligand, 5\u2010(4\u2010piperidyl)isoxazol\u20103\u2010ol (4\u2010PIOL). The action of 4\u2010PIOL was compared with that of the established GABA<jats:sub>A<\/jats:sub> agonist, isoguvacine.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>With a symmetrical Cl<jats:sup>\u2212<\/jats:sup>gradient across the membrane and a holding potential of \u221260 mV, both isoguvacine and 4\u2010PIOL evoked an inward current. The reversal potentials of the responses to both agents were identical (+8.8 mV, <jats:italic>n<\/jats:italic> = 4) and the current\/voltage relationships showed outward\u2010going rectification.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The response to 300 \u03bc<jats:sc>m<\/jats:sc> 4\u2010PIOL was completely blocked by the GABA<jats:sub>A<\/jats:sub> antagonist, bicuculline methobromide (BMB, 10 \u03bc<jats:sc>m<\/jats:sc>). The pA<jats:sub>2<\/jats:sub> of BMB was &gt;6.46. With 2 m<jats:sc>m<\/jats:sc> 4\u2010PIOL about 15% of the response remained in the presence of 100 \u03bc<jats:sc>m<\/jats:sc> BMB. This may represent a non\u2010specific component of the response to large concentrations of 4\u2010PIOL.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>4\u2010PIOL was about 200 times less potent as an agonist than isoguvacine. Because of the rapid fade (desensitization) of isoguvacine\u2010induced currents, the maximum response to this agonist was not determined. However, the response to 2 m<jats:sc>m<\/jats:sc> 4\u2010PIOL was only a small fraction of that evoked by submaximal concentrations of isoguvacine.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Setting the response to 1 m<jats:sc>m<\/jats:sc> 4\u2010PIOL as maximum, the EC<jats:sub>50<\/jats:sub> for 4\u2010PIOL was 91 \u03bc<jats:sc>m<\/jats:sc> (95% confidence limits: 73\u2013114 \u03bc<jats:sc>m<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>4\u2010PIOL antagonized the response to isoguvacine with a parallel shift to the right of the dose\u2010response curve. The antagonist action of 4\u2010PIOL was about 30 times weaker than that of BMB. When allowance was made for the intrinsic agonist action of 4\u2010PIOL, the <jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub> was 116 \u03bc<jats:sc>m<\/jats:sc> (95% confidence limits: 102\u2013130 \u03bc<jats:sc>m<\/jats:sc>). This was not significantly different from EC<jats:sub>50<\/jats:sub> (<jats:italic>P<\/jats:italic> = 0.86; non\u2010parametric Mann\u2010Whitney test).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>It is concluded that 4\u2010PIOL is a partial agonist at the GABA<jats:sub>A<\/jats:sub> receptor on cultured hippocampal neurones.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p>","DOI":"10.1111\/j.1476-5381.1991.tb12389.x","type":"journal-article","created":{"date-parts":[[2012,7,20]],"date-time":"2012-07-20T06:46:04Z","timestamp":1342766764000},"page":"85-90","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Electrophysiological studies of the GABA<sub>A<\/sub> receptor ligand, 4\u2010PIOL, on cultured hippocampal neurones"],"prefix":"10.1111","volume":"104","author":[{"given":"U.","family":"Kristiansen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.D.C.","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Falch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Krogsgaard\u2010Larsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,7,19]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)90144-3"},{"key":"e_1_2_1_3_1","first-page":"261","article-title":"Synthesis and biological activity of a GABA\u2010A agonist which has no effect on benzodiazepine binding and structurally related glycine antagonists","volume":"1","author":"BYBERG J. 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